Human hepatocytes are valuable tools for hepatotoxicity screening, a crucial step for drug discovery and development. In addition, hepatocyte transplantation has proved to be a promising alternative to orthotropic liver transplantation. The current cellular system of choice for drug screening and cell therapy is primary human hepatocyte (PH). However, the utility of primary human hepatocyte in either clinical or pharmaceutical applications is limited by their availability, donor variability, limited proliferation and decline in function over extended culture periods. Therefore, substantial effort has been put into the derivation of alternative expandable sources of functional hepatocytes which can counteract the disadvantages associated with primary human hepatocyte.
Human embryonic stem cells (hESCs) provide an attractive alternative cell source to primary human hepatocyte, due to their unlimited proliferative and pluripotent differentiative capacity. Accordingly, there is a need to provide for a method for obtaining and maintaining hepatocyte-like cells that represent adult hepatocytes phenotype.